Success in Neglected Disease Research Leads to a Broad Alliance -- UPDATE

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Canada , Topic: Discovery/Development , United States

[NOTE: This is an UPDATE to a case study initially published in 2009. Read the original case study for appropriate context.]

In 1999, University of British Columbia (UBC) Professor Kishor Wasan, Ph.D., took on the challenge of reworking the drug Amphotericin B (“AmpB”) into an effective, tropically stable oral form to treat the parasitic disease visceral leishmaniasis. During that process he found himself immersed in more than a decade of laboratory research, support from the Bill & Melinda Gates Foundation, a partnership with the Consortium for Parasitic Drug Development (CPDD) at the University of North Carolina and animal studies conducted with scientists at The Ohio State University. A licensing agreement for his AmpB work was signed with Vancouver-based iCo Therapeutics, Inc. in 2008.

In 2010, Wasan’s team announced a significant milestone: a tropically stable oral AmpB version that proved more than 96 percent effective in reducing the disease in animal studies. Also in 2010, iCo’s formulation for treating visceral leishmaniasis received “orphan drug” designation by the U.S. Food & Drug Administration (FDA), an important recognition of its promise.

A far different milestone also grew out of Wasan’s work: creation of the university’s Neglected Global Diseases Initiative (NGDI) as an organization to aid scientists from a broad range of disciplines in advancing neglected disease research and implementation in developing countries.

“It’s a grassroots alliance that brings many diverse people—from bench scientists to medical practitioners—together under a single umbrella to assist them with research, with fundraising and with increasing awareness of neglected diseases,” says Wasan, a professor of pharmaceutical sciences who serves as NGDI’s director. As 2012 began, membership encompassed nearly 300 faculty and students. Organizational and project partners range from UBC’s Faculty of Pharmaceutical Sciences to the Gates Foundation.

Leishmaniasis and AmpB

As a neglected disease found around the world, from Central American rainforests to Middle Eastern deserts, leishmaniasis gets little attention in North America and Europe. The World Health Organization estimates that it afflicts some 12 million people in 88 countries.

Caused by a parasitic protozoan called Leishmania, leishmaniasis is transmitted by the bites of sand flies. The more-common cutaneous form causes ulcerations on the skin, including permanent, disfiguring facial scarring. The blood-borne visceral form, which infects internal organs like the liver and spleen, is less common but, if untreated, always fatal. It’s estimated that worldwide some 500,000 people develop new cases of visceral leishmaniasis (VL) annually, and that more than 50,000 people die from it each year.

Amphotericin B was known to be effective for treating leishmaniasis when Wasan started working with it as a treatment for fungal infections. While its oral form wasn’t effective on VL, its injectable version was—but with significant drawbacks. It’s highly toxic to kidneys, using it involves infusions that take several hours and it doesn’t remain stable in the hot climates where leishmaniasis is most often found. A less-toxic variation called Ambisome had been developed, but it was only available in an injectable formulation. 

Wasan was giving a talk in 1999 about his Amphotericin B work on fungal infections when he was asked if the drug could be reformulated into a tropically stable oral medication for VL. Such a medication could be important—less expensive to manufacture, easier to transport and store, far more feasible for less-trained personnel to administer in rural areas where treatment is currently unavailable.

Wasan didn’t think it could be done but he was intrigued. By 2007, he had an oral form that was much less toxic, but not one that was tropically stable. He submitted a grant request to the Gates Foundation and they hooked him up with the CPDD, providing funding for the work through CPDD.

The 2008 agreement with iCo Therapeutics was the first signed in accordance with UBC’s Global Access Principles, laying out standards for maximizing the impact of UBC-developed technologies in the developing world. “The AmpB agreement provided a win-win model,” notes Ian Bell of UBC’s University-Industry Liaison Office. “iCo is helping develop a leishmaniasis formulation accessible to developing countries while receiving worldwide rights to create an anti-fungal form of AmpB for sale in the developed world.”

The team succeeded in developing a lipid-based AmpB formulation that was stable for 60 days at 42 degrees C (109 degrees F)—but requiring two doses a day. The Gates Foundation wanted to get it down to one. Further animal studies at Ohio State showed a 96 percent reduction in the disease with a one-dose formula used for five days. Wasan and his colleagues published their results in the PLoS journal Neglected Tropical Diseases in December, 2010.

AmpB’s FDA designation as an “orphan drug” also came in 2010.  Not only does it indicate that the agency sees AmpB as a valid potential treatment for leishmaniasis, Wasan notes, the designation enables tax credits that can reduce the costs of clinical trials.

The next challenge is conducting Phase I human trials – and first raising $5 million to support them. These are tough times to find funding, Wasan says, but the university and iCo are working diligently to accomplish it.

The Neglected Global Disease Initiative

Creation of the Neglected Global Diseases Initiative was sparked by a random thought that crossed Wasan’s mind during his leishmaniasis research. “I was alone in my lab and I wondered how many other people were working in relative isolation at UBC on neglected diseases?” he says. “It turned out to be far more than I thought.”

It was a broad constituency, as diverse as scientists involved in drug development, physicians concerned with international health systems, and specialists focused on nutrition in developing countries.

Wasan was among 15 faculty and students who founded the organization in June of 2009, with Wasan named director. Today, membership encompasses 80 principal investigators and more than 200 students, from undergraduates to post-doctoral fellows. Partner organizations include UBC’s Faculty of Pharmaceutical Sciences, the University-Industry Liaison Office, the student group Universities Allied for Essential Medicines (UAEM), the Centre for Drug Research and Development, Mitacs, Inc., the CPDD and the Bill & Melinda Gates Foundation. UAEM, with chapters on multiple campuses across North America, played a significant role in UBC’s adoption of the Global Access Principles. Mitacs is non-profit foundation that supports education and research in Canadian universities.

NGDI projects have included a Neglected Global Diseases Symposium in 2010 and a Distinguished Lectureship Seminar Series that features noted speakers every several months. As of the end of 2011, some $16 million had been raised for neglected disease projects under the NGDI banner, including multi-million dollar grants from the Gates Foundation to support work in preventing and treating pre-eclampsia; from the Canadian Institutes of Health Research to focus on health issues related to the global food system and on issues affecting the health of international health workers; and from the Canadian International Development Agency to improve the survival rates of Bangladeshi mothers, newborns and young children through the prevention of sepsis.

NGDI’s vision extends beyond straightforward bench research. “Research in the medical aspects of neglected diseases is extremely important,” Wasan says, “but it’s equally important to deal with weak health systems and social and environmental conditions in developing countries that perpetuate disease.

“Our focus extends beyond drug development and delivery to effective disease-reducing implementations.”

By Ralph Fuller

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